الفهرس 
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Abstract
Lipotoxicity is a term that can be used to summarize all the metabolic derangements which are associated with excess unhealthy fat accumulation. Furthermore, an underlying silent chronic inflammatory process that provokes all deleterious chronic consequences of lipotoxicity, is the main underlying player that need much more attention. The importance of studying such issues in Egypt comes from the fact that our country carries the highest epidemiological burden of obesity and lipotoxicity worldwide with highest percentage of obese adults being present in Egypt.
In fact, the factors that contribute to obesity and lipotoxicity expansion are continuing and this refers to the need to urgent strategies to reverse or prevent the progression of complications associated with these conditions. There are different approaches which may have a beneficial effect to hamper the associated inflammatory process including pharmacological and nutritional interventions that have antiinflammatory properties with different mechanisms.
In view of such consideration, the present study was designed to evaluate the protective effects of celecoxib, anti-inflammatory nutrition and safranal on the development and progression of lipotoxicity induced by HFD in rats.
The study was conducted on 64 male albino rats of body weight ranging from 150-200 grams:
They were divided into eight groups, each of eight rats:
1. group Ι (Normal control group):
These animals were fed standard rat chow (7.2% fat) throughout the study period (8 weeks).
2. group ΙΙ (High fat diet (HFD) control group):
It served as control group for group III.
Animals in this group were fed with in-house prepared unspecified high-fat diet (HFD) (58% calories as fat) throughout the study period (8 weeks).
3. group ΙΙI (ω-6 HFD control group): Received HFD enriched with ω-6 polyunsaturated fatty acid (PUFA) for 8 weeks.
4. group ΙV (ω-3 HFD supplemented group) or (anti-inflammatory diet group): Received ω-6 HFD enriched with ω-3 (PUFA) with ratio (3:1) for 8 weeks.
5. group V (Celecoxib supplemented-HFD group):
Received ω-6 HFD in the same regimen and for the same duration like group ΙΙI supplemented with a selective COX-2 inhibitor (celecoxib) in a dose of 30 mg/kg once daily.
6. group VΙ (Safranal supplemented-HFD group):
Received ω-6 HFD in the same regimen and for the same duration like group III supplemented with safranal in a dose of 0.75 mg/kg once daily.
Combinations groups:
7. group VΙΙ (anti-inflammatory diet + Celecoxib):
Received anti-inflammatory diet & celecoxib as previously mentioned in group ΙV &V.
8. group VΙΙΙ (anti-inflammatory diet + Safranal):
Received anti-inflammatory diet & safranal as previously mentioned in group ΙV & VΙ.
At the end of the study period (8 weeks), twenty-four hours after the last treatment, the animals were assessed as regards the following anthropometric measurements: (BMI and AC). And then they were anesthetized by ether and blood samples were collected for assessment of these parameters: serum IL-6 concentration, TGF-β1 concentration and AA/EPA ratio in the RBCs. Strips of the aortic tissue were cut and fixed in buffered 10% formalin. They were processed for routine paraffin block preparation. Sections of 5μmm were cut by rotatory microtome and stained with haematoxylin and eosin stain (H&E), and then they were examined under the light microscope for histological changes.
Results of the present work revealed that, there was a statistically significant increase in serum IL-6 concentration and AA/EPA ratio in RBCs in unspecified HFD group (group II) & ω-6 HFD group (group III) as compared to normal control group (group I). Comparing the results of groups II & III revealed insignificant increase in IL-6 concentration and AA/EPA ratio in group III. Also, there was a significant decrease in serum TGF-β1 concentration in groups II & III as compared to group I. Comparing the results of groups II & III resulted in insignificant decrease in serum level of TGF-β1 in group II.
Administration of the anti-inflammatory diet (group IV) had a significant decrease in AA/EPA ratio in RBCs, insignificant decrease in serum IL-6 concentration and insignificant increase in serum TGF-β1 concentrations in comparison to groups II&III.
On the other side, administration of celecoxib (group V) had a significant decrease in both serum IL-6 concentration and AA/EPA ratio and a significant increase in serum TGF-β1 in comparison to groups II&III. And administration of safranal (group VI) had insignificant effect on IL-6, TGF-β1 concentrations and blood level of AA/EPA ratio in RBCs in comparison to groups II&III.
The combination groups of (celecoxib + anti-inflammatory diet) group (VII) and( anti-inflammatory diet + safranal)group (VIII) significantly decreased both serum IL-6 concentration, AA/EPA ratio in RBCs and increased serum TGF-β1 concentration in comparison to group II&III. The best recorded results were for (group VII) with significant difference between this group and groups IV,V,VI,VIII.
In addition, there was a statistically significant improvement in both AC and BMI only in the combination groups of (celecoxib + anti-inflammatory diet) or (anti-inflammatory diet + safranal) in comparison to groups II&III.
Histopathological examination for aortic tissue also confirmed that the protective effects of the combination groups were better than the sole administration of celecoxib or anti-inflammatory diet or safranal by amelioration of signs of inflammation and endothelial dysfunction that were represented by detachment in the endothelium and sub endothelial infiltration of inflammatory cells in both ω-6 HFD group and unspecified HFD group with great improvement of the architecture of the aortic tissue.